Response to CFTR Modulators in CF Patients Under 18 Years (MODUL-CF)
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| ClinicalTrials.gov Identifier: NCT04301856 |
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Recruitment Status :
Recruiting
First Posted : March 10, 2020
Last Update Posted : March 22, 2021
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CFTR modulators should improve the prognosis of Cystic Fibrosis. Identifying patients under the age of 18 responding to CFTR modulators as well as detecting possible toxicity is an important medical objective given the potential side effects and the high cost of these molecules.
This observational follow-up cohort study is carried out as part of routine care.
The main objective is to assess the evolution of pulmonary structural impairment by low-dose CF scan at the end of the first year of CFTR modulator therapy.
The secondary objectives are to evaluate structural impairment at low dose scan at 3 years and 5 years of CFTR modulator treatment, the evolution of respiratory functional parameters, growth, puberty, lung infection, sweat test, quality of life and pancreatic function, as well as tolerance of modulators including liver toxicity.
| Condition or disease | Intervention/treatment |
|---|---|
| Cystic Fibrosis in Children | Drug: CFTR Modulators |
Cystic fibrosis (CF) is a deadly disease. This is due to overinfected chronic obstructive pulmonary disease that progresses to end-stage respiratory failure. CFTR modulators should improve the prognosis of CF, as they may slow the progression of patients' lung disease. Assessing their impact in the paediatric population is becoming a major issue. Children and adolescents under the age of 18 are a target cohort because they have a lung disease that is still poorly developed. Early prescription of CFTR modulators is therefore a priority but requires evidence of absence of toxicity. Identifying patients under the age of 18 responding to CFTR modulators as well as detecting possible toxicity, is an important medical objective given the potential side effects and the high cost of these molecules.
The outcomes previously used in Phase III studies (FEV1, frequency of exacerbations, nutritional status) are insufficiently sensitive in this population.
Other criteria need to be analyzed to identify the response to CFTR modulators in the short and medium term. The investigators hypothesize that the assessment of pulmonary structural impairment by low-dose lung CT-scan as part of routine care could be a much more sensitive criterion for the development of lung disease under CFTR modulators.
This observational follow-up cohort study is carried out as part of routine care. It does not involve a specific collection for research. Excess bronchial secretions and blood will be kept instead of being discarded in the event of a possible requalification for research.
The main objective is to assess the evolution of pulmonary structural impairment by low-dose CF scan at the end of the first year of CFTR modulator therapy The secondary objectives are to assess following criteria
- Tolerance of modulators in this age group, including screening for bronchial reactivity at treatment, early liver toxicity
- Longitudinal evolution of pulmonary structural impairment by low dose scan at 3 years and 5 years of CFTR modulator treatment
- Evolution of respiratory functional parameters
- Measurement by spirometry and plethysmography
- Lung clearance index (if possible)
- Longitudinal evolution of bacterial colonization, compared to the year prior to modulating treatment
- Exacerbations: number, duration, days of antibiotics, hospitalizations, return to stable condition
- Colonization of bronchial secretions
- Changes in quality of life
- Evolution of the sweat test
- Longitudinal evaluation of pancreatic function
- Longitudinal evaluation of growth and puberty compared to the year prior to CFTR modulator
- Growth speed, and bone age
- Bone mineralization, body composition (if possible)
- Pubertal markers from 9 years in girls and 10 years in boys
- Evaluation of glycemic dysregulation if present
- Preservation of samples taken as part of routine care (serum, bronchial secretions) for possible research use
| Study Type : | Observational |
| Estimated Enrollment : | 600 participants |
| Observational Model: | Cohort |
| Time Perspective: | Prospective |
| Official Title: | Evaluation of the Response to CFTR Modulators in Patients With Cystic Fibrosis Less Than 18 Years of Age |
| Actual Study Start Date : | January 1, 2020 |
| Estimated Primary Completion Date : | July 1, 2025 |
| Estimated Study Completion Date : | January 1, 2026 |
| Group/Cohort | Intervention/treatment |
|---|---|
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CF children treated with CFTR modul
Cystic fibrosis patients under 18 years treated with CFTR modulators according to french health recommendations observational cohort study
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Drug: CFTR Modulators
CFTR modulators as recommended in routine care by the french health authorities
Other Name: Orkambi, Kalydeko... |
- Lung Imaging [ Time Frame: at initiation, as part of national guidelines ]Lung structural injury assessed by Low Dose CT, as part of routine care
- Lung Imaging [ Time Frame: at 1 year, as part of national guidelines ]Lung structural injury assessed by Low Dose CT, as part of routine care
- Lung Imaging [ Time Frame: at 3 years, as part of national guidelines ]Lung structural injury assessed by Low Dose CT, as part of routine care
- Lung Imaging [ Time Frame: at 5 years, as part of national guidelines ]Lung structural injury assessed by Low Dose CT, as part of routine care
- weight in kilogrammes [ Time Frame: longitudinal monitoring of assessments carried out as part of routine care during 5 yrs ]weight in kilogrammes (associated with a retrospective collection in the year prior to treatment)
- height in meters [ Time Frame: longitudinal monitoring of assessments carried out as part of routine care during 5 yrs ]height in meters (associated with a retrospective collection in the year prior to treatment)
- pubertal evolution [ Time Frame: longitudinal monitoring of assessments carried out as part of routine care during 5 yrs ]pubertal evolution (associated with a retrospective collection in the year prior to treatment)
- bronchial infectious exacerbations [ Time Frame: longitudinal monitoring of assessments carried out as part of routine care during 5 yrs ]bronchial infectious exacerbations (associated with a retrospective collection in the year prior to treatment)
- Forced Expiratory Volume in 1 second(FEV1) [ Time Frame: longitudinal monitoring of assessments carried out as part of routine care during 5 yrs ]Forced Expiratory Volume in 1 second(FEV1) in liter
- Forced Vital Capacity (FVC) [ Time Frame: longitudinal monitoring of assessments carried out as part of routine care during 5 yrs ]Forced Vital Capacity (FVC) in liter
- Force Expiratory Flow 50 (FEV50) [ Time Frame: longitudinal monitoring of assessments carried out as part of routine care during 5 yrs ]Force Expiratory Flow 50 (FEV50) in liter
- Forced Expiratory Flow 25-75 (FEV25-75) [ Time Frame: longitudinal monitoring of assessments carried out as part of routine care during 5 yrs ]Forced Expiratory Flow 25-75 (FEV25-75) in liter
- Residual Volume (RV) [ Time Frame: longitudinal monitoring of assessments carried out as part of routine care during 5 yrs ]Residual Volume (RV) in liter
- Total Pulmonary Capacity [ Time Frame: longitudinal monitoring of assessments carried out as part of routine care during 5 yrs ]Total Pulmonary Capacity in liter
- Lung Clearance Index - Lung Clearance Index [ Time Frame: longitudinal monitoring of assessments carried out as part of routine care during 5 yrs ]Lung clearance of nitrogen
- colonization of bronchial secretions [ Time Frame: longitudinal monitoring of assessments carried out as part of routine care during 5 yrs ]bacteria, fungi, mycobacteria
- quality of life questionnaire [ Time Frame: longitudinal monitoring of assessments carried out as part of routine care during 5 yrs ]CFQ questionnaire for children above 8 years: worse 0, better 100
- ENT quality of life questionnaire [ Time Frame: longitudinal monitoring of assessments carried out as part of routine care during 5 yrs ]SN-score: better score 1, worse 7
- Abdominal quality of life questionnaire [ Time Frame: longitudinal monitoring of assessments carried out as part of routine care during 5 yrs ]better score: 0, worse: 25
- liver ultrasound [ Time Frame: longitudinal monitoring of assessments carried out as part of routine care during 5 yrs ]liver ultrasound
- elastometry (data available in centers with the necessary equipment) [ Time Frame: longitudinal monitoring of assessments carried out as part of routine care during 5 yrs ]elastometry (data available in centers with the necessary equipment)
- sweat test [ Time Frame: longitudinal monitoring of assessments carried out as part of routine care during 5 yrs ]sweat collection
- serum and fecal pancreatic biological markers [ Time Frame: longitudinal monitoring of assessments carried out as part of routine care during 5 yrs ]immunoreactive trypsin, lipase, amylase, vitamin A and E, Prothrombin time, and fecal (fecal elastase
- bone biological markers [ Time Frame: longitudinal monitoring of assessments carried out as part of routine care during 5 yrs ]25OHvitD, Ca, P, PTH, Osteocalcin, IgF1, IgF1BP3, CTX
- bone maturation [ Time Frame: longitudinal monitoring of assessments carried out as part of routine care during 5 yrs ]Zscore (in relation to height and sex and weight) (data available in centers with the necessary equipment)
- puberty [ Time Frame: longitudinal monitoring of assessments carried out as part of routine care during 5 yrs ]serum dosage of FSH, LH, Estradiol, testosterone Pelvic ultrasound if puberty initiated in girls
- intestine inflammation [ Time Frame: longitudinal monitoring of assessments carried out as part of routine care during 5 yrs ]fecal Calprotectine
- glycemic regulation [ Time Frame: longitudinal monitoring of assessments carried out as part of routine care during 5 yrs ]monitoring of glycemic dysregulation ( as routinely done in the centers)
- side effects: declarative collection and monitoring [ Time Frame: longitudinal monitoring of assessments carried out as part of routine care during 5 yrs ]declarative collection and monitoring
Biospecimen Retention: Samples Without DNA
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| Ages Eligible for Study: | up to 18 Years (Child, Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
| Sampling Method: | Non-Probability Sample |
Inclusion Criteria:
Children with cystic fibrosis under the age of 18 under CFTR modulator therapy
Exclusion Criteria:
- Patients with cystic fibrosis without indication for CFTR modulator therapy
- Patients over the age of 18
- Pregnant or lactating women
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04301856
| Contact: Stéphane Mazur, PhD | 0033427855043 | stephane.mazur@chu-lyon.fr | |
| Contact: Anne-Sophie Bonnel, MD | OO33144494887 | asbonnel@ch-versailles.fr |
| France | |
| Sermet-Gaudelus Isabelle | Recruiting |
| Paris, France, 75015 | |
| Contact: Isabelle Sermet-Gaudelus, MD PhD 0033687078403 isabelle.sermet@aphp.fr | |
| Principal Investigator: | Isabelle Sermet-Gaudelus, MD PhD | Société Francaise de la Mucoviscidose |
| Responsible Party: | Isabelle SERMET-GAUDELUS, Professor Isabelle Sermet-Gaudelus, Societe Francaise de la Mucoviscidose |
| ClinicalTrials.gov Identifier: | NCT04301856 |
| Other Study ID Numbers: |
0011928 |
| First Posted: | March 10, 2020 Key Record Dates |
| Last Update Posted: | March 22, 2021 |
| Last Verified: | March 2021 |
| Studies a U.S. FDA-regulated Drug Product: | No |
| Studies a U.S. FDA-regulated Device Product: | No |
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Cystic Fibrosis Fibrosis Pathologic Processes Pancreatic Diseases Digestive System Diseases |
Lung Diseases Respiratory Tract Diseases Genetic Diseases, Inborn Infant, Newborn, Diseases |